JPH03287571A - New sulfonyl compound and production thereof - Google Patents

Abstract

NEW MATERIAL:A sulfonyl compound expressed by formula I (R and R' are H,-COCHR,-COCR,-SO2CH3,-CO2C2H5,-CH2CH2R<4>-CH2CH2OH-CONHCH2CH2R<4>, etc.; R<4> is Cl, formula II, etc.; R<1> and R<2> are amine such as formula III or -NHCH2CH2Cl, hydroxyl such as -O-CH3,-O-CH2-CH3 or -O-CH2-CH2-CH3 or ether such as ClCH2OCH2Cl). EXAMPLE:A compound expressed by formula IV. USE:Useful as a polymer coordination complex or for formulations containing the aforementioned compound as an active ingredient with powerful clathration action and providing beautiful crystals by clathration of even substances in any forms. Furthermore the above-mentioned compound is a readily water-soluble and crystalline hybrid compound suitable for the formulations and slowly released in the living bodies without any aide effects. PREPARATION:For example, as shown in the reaction formulas, a compound expressed by formula IV in formula I is obtained from 4- carbethoxyaminobenzenesulfonyl chloride and 2-aminoethanethiol.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing a sulfonyl compound, a polymeric coordination complex thereof, a method for producing the same, and a method for producing a preparation containing the active substance. has the following general structural formula 1.

In the diagram, R and R' are hydrogen -COCHR24, -COCR
24, -SO2CH3, -CONHCH2COOC2H
5 or CH2CH2OCNH2.

R4 represents Cl or a compound of the following formula.

-NHCO2CH2CH2OH, -NHCO2C2H5, -NHOH, -NHCONH
Oder-NHCH3R and R' are the same compound or have different structures.

In the formula, R1 and R2 are (1) amine-NHCH2CH2Cl, -NHCONHOH, -NH
CO2C2H5, 6-Mercaptopurinyl
, 5-Fluoruracilyl, or Predni
solyl, Salicylhydrorazidyl
, 1-Allyl-2-thiouracilyl, H
ydroxylamin, Isomidyl or Met
iyl Hydroxylamin (2) Hydroxy
l -O-CH3, -O-CH2-CH3, -O-CH2-
CH2-CH3, -O-C6H5-O-CH2-CH-
CH2 or Bezhydorl (3) Ether ClCh2-OC2H5, OHCH2CH2-O-CH
2CH2Cl, ClCH2CHCl-OC2H5 ether forms Oxonium salt with sulfonyl chloride.

(4) R1 R2 represents an inorganic compound -(Na)SH-(Na)F, -(X)I. Others (5) R1 R2 is -(Na)N3 or -C,C-(Cl)3 The general formula (1) can be replaced with alkanesulfonyl chloride (11), or both can be mixed and combined.

The diagram (■) represents a linear hydrocarbon, Mw(S)i, and the number of the carbon chain indicates the position of the side chain (substituter).

The group shown in general scheme (1) is substituted with a halogenalkyl group or an aminomethyl group. In the case of aminomethyl group, it has the following structural formula.

Mt shown in general scheme (1) represents metal.

As shown in Scheme 1, the functional group of sulfamine can be converted into a modified metal salt through various substitutions.

This is equally a control of the present invention.

However, what is extremely interesting in this case is that during the salt formation, the ionic nucleophilic substitution reaction between both the sulfamine and the metal salt is accompanied by an ionic interaction (metenaction) with one or multiple salt constituent molecules selected at the same time. This means that a polymer complex (clathrate) is formed.

Valid guest compounds included at that time include, for example, the anticancer drugs nitromine, cyclophosphamide, thiotepa, 6-mercaptopurine, 5-fluorouracil, buinplastin, alpha-asparaginase or prednisolone; Antibiotics such as chloramphenicol, streptomycin or penicillin, medically effective pigments such as pioctanin (methyl violet), methylene blue or acriflapine, general organic compounds salutyl hydratide, thiodinamine, glycoseed, chlorpheniramine α-milenate, Abscisic acid, cytosine, N-methylformamide, urethane, quinone, methylhydroxyamine, carbamate or 2-chloroethyl conductors, herbal extracts, etc. Inorganic substances Zn, Cu, Hg and Pt salts, etc. Enzymes hyalunitase, lysozyme, collagenase, sulfatase, etc. Hormones Pred ni
bolone, Hydro Cortison, betamethasone, etc.

Regarding the mechanism of the above-mentioned inclusion phenomenon, in order to make it easier to understand, the details will be described below.

Sulfamine is acidic and forms salts through acid-base reactions.

Nucleophilic substitution reaction
n) At the time of salt formation, a strong ion exchange reaction occurs between the sulfonyl group and the metal salt, and an electric field is created between the two sulfamine groups, causing one or several molecules to
r Incorporated into Space.

In the Inter Space, various ionic bonds, various ionic interactions, Wanderworth force, etc. work together in concert with the Donin-Acceptor Besis, resulting in the production of a very strong hybrid compound. In this case, this environment does not occur with a single sulfonyl group. so-called bifunction
It has now been proven that the effect of al. This is H
Explained by the chemistry of ost and gest.

In 1977, Wulf and Shea of West Germany made an epoch-making announcement that they could artificially design a three-dimensional space with a certain shape and size inside a polymer and use it to selectively take in substances. It can be said that this achievement shows a clear basis for solving problems in inclusion chemistry.

Bifunctional aggregation reaction according to the present invention
Codensation) is carried out smoothly in a polar solvent with sulfamine alone or together with one or several inclusion molecules each having a different action. The flocculants used in this case are alkali and alkaline earth or heavy metal salts. Magnesium sulfide is particularly commonly used.

The inclusion effect according to the present invention is extremely strong and can be applied indiscriminately to fluids, sludge, sticky or unstable compounds, or insoluble compounds such as ZnO, and others that cannot be formulated. Regardless of the form, beautiful crystals can be created by including things that were considered neglected.

And it is a crystalline hybrid compound that is extremely soluble in water and suitable for formulation. Even toxic substances are included within the polymer and are gradually released and act within the body, with almost no side effects observed. Everything that smells and has color disappears.

This, in addition, combined with the deliberate substitution and incorporation of the sulfamine functional groups results in a strong hybrid compound with proportional ionic bonding of the functional groups.

When producing a complex according to the present application, the gest compound and sulfamine are combined according to their functional properties, so complexes with different effects can be obtained.

For cancer cells and those with abnormally strong resistance such as Virms, a combination of several functional groups with strong effects has been used, but it has not yet been possible to eradicate the remaining cells.

Complex mix using drugs in combination, not just cancer drugs
Knowledge that can be used as ture has been available in human history since ancient times.

It is expected that a drug combination therapy with proven efficacy will emerge.

In the present invention, liquid or syrup-like substances and solid substances, which have not been considered until now, are included equally and indiscriminately to form a hybrid.
ng, and created an extremely effective water-soluble hybrid, opening up a new avenue for treatment.

Since 1969, the compound of the present invention has been continuously used as a Nat.
ional Cancer Institute of
America. Screening tests are being conducted systematically with the cooperation of As a result, it was confirmed in animal experiments that this compound has anticancer properties, and it was also proven that it has almost no toxicity.

Next, clathrate compounds were prepared in accordance with the present application, tested against cancer cells, and found to have certain effects, which were generally divided into 10 types and are shown below.

(1) Anticancer drugs nitromine, cyclophosphamide, thiotepa, 6-
Mercaptopurine 5-fluorouracil, vinblastine, α-asparaginase prednisolone, or CH(
NHCH2CH2CL) 3 (2) Antibiotics such as chloramphenicol, streptomycin or penicillin.

(3) Medically effective pigments such as pioctanin (methyl violet), methylene blue or acriflapine.

(4) General organic compounds salutyl hydratide, thiodinamine, glycoseed,
Quinoneimine α-chlorpheniramine maleate, abscisic acid, cytosine, N-methylformamide, urethane and ethyleneimine, herbal extract.

(5) Inorganic substances Zn, Cu, Hg and Pt salts, etc. Other Pd and Au
etc.

(6) Nitroso compound (CH3)2N-NO (C2H5)2N-NO The nitroso compound used in this application can be obtained as follows.

3 ml N-methylformamide, 15 ml glacial acetic acid, 6
18 g of sodium nitrite was added little by little to 0 ml of acetic anhydride with stirring, and the mixture was left at room temperature overnight. Then, when alcohol is added thereto and the filtrate is dried under reduced pressure, a nitroso compound is obtained.

(7) Tetra-2 (chlorethyl) amino
)-o-quinone(Tetra(N-mathy
l-N-formyl)amino)-o-quino
ne(Tetra(N-carboethoxy)am
ino)-o-quinone(Tetra(N-az
iridino))-o-quinone(Tetra
(N-methyl-N-hydroxyl)amine
o)-o-quinone or p-quinone
, the O,P-chloroanyl compound of the present application can be obtained as follows.

Dissolve 1 g of commercially available chloranil in 20 ml of pyridine, gradually add 0.4 g of primary or secondary amine, leave it at room temperature overnight, then add petroleum ether, and the desired compound becomes a sticky substance. It precipitates as This material is then thoroughly washed with petroleum ether and dried before use.

(8) Enzymes hyaluronidase, lysozyme, collagenase, sulfatase, and other immobilized enzymes, especially metalloenzymes (9) Hormones such as prednisolone, hydrocortisone, or betamethasone.

(10) Carbamate esters NH2cOOCH2OH2Cl, NH2COOCH2C
(Cl)3, HS. CH2CH2O-OC. NH2 (11) 2-chloroethyl compound Cl-CH2・CH2-O-CH3, Cl-CH2CH2-NH-OH, (12) Ether compound CH3-O-CHCl2・ClCH2-OC2H5・O
HCH2CH2-O-CH2CH2Cl・ClCH2C
HCl-OC2H5 ether forms oxonium salts with sulfonyl chlorides.

(C2H5)2O+HCl→((C2H5)2o+-H
) The chlorinated compound obtained in Cl-
1R2 can be smoothly substituted with the equivalent amount of substituent described in 1R2 in 10-20 times the amount of pyridine solution at room temperature.

After this mixture is left to stand overnight, petroleum ether, riboin, etc. are added to it, and the compound becomes oily and precipitates at the bottom of the vessel. This is separated and used.

The resulting compound has the following structural formula.

Next, in order to substitute R in the N- group of general formula (1), the N- compound obtained above must first be hydrolyzed.

Carbethoxy groups are more easily hydrolyzed than acetyl groups.

When 20 times the amount of 10% NaCH is added to this carbethoxy compound and heated for 15 minutes in an aqueous solution, it is easily hydrolyzed and NH2 groups are liberated as shown in the following formula.

Next, the compound of general formula 1 is induced into a complex directly or with a metal salt solution in an organic solvent that has cohesive properties with the gest compound.

2-Methoxyethanal is suitable as a solvent.

In order to produce the compound of the present application, P-A is used as a starting material.
cetaminobenzensulfonylchl
oride or commercially available Alkansulfonylch
Use loride.

Or Phenyluret of the following formula which is easily hydrolyzed
han and acetylbenzylamine are used after being chlorosulfonated.

To produce this, take 250g of chlorosulfuric acid and 1
50 g of phenyl urethane is gradually added at a temperature below 0° C., and the mixture is heated to 50° C. for several hours. When this is poured onto ice water, a compound of the following formula is obtained.

Similarly, halogen or alkylated benzene can be easily converted into chlorosulfonate and used in the present application.

The liberated NH2 groups are easily chloroacetylated in pyridine solution. To this product, an equimolar amount of dichloroacetyl chloride or trichloroacetyl chloride is added dropwise to 20 times the amount of pyridine at 10° C. or lower. Then leave it at room temperature overnight. When this mixture is then poured onto ice water, a compound of the following formula is obtained.

When combining 2 equimolar amounts of chloride, the compound has 1
It must be heated in a closed tube at 60°-180°C for 1-2 hours. When the mixture is poured onto ice water, a compound of the following formula is obtained.

Instead of acetyl chloride, the corresponding anhydrous chloroacetyl chloride or isocyanate can be used in this case. To do this, a small amount of benzol is added to a compound having a free NH2 group, and then when an equivalent amount of 2-cheorethyeisocyanate is added, a violent reaction occurs and the compound is combined to obtain a compound as shown in the following formula.

In addition, 30 ml of 3 g of a compound having a free 4-NH2 group
To this, 6 ml of ethylene oxide and 6 ml of distilled water were added, and the mixture was heated to 30° C. for 2 hours in a closed tube. Thereafter, when petroleum ether is added to this, a compound having the structure of the following formula is separated.

In this case, A1Ky1emo is used instead of ethylene oxide.
xide is also used. Moreover, this OH group can be easily converted into chloride.

To clize the compound IV above, add it to Benzene.
Chlorination can be easily carried out when an equivalent amount of thionyl chloride is added dropwise to the solution dissolved in E and added with a small amount of pyridine and heated.

The compound has the structure:

Example 2 2 g of carbetoquin aminobenzenesulfonyl clotide and 1 g of salutyl hydratide are dissolved in 30 ml of pyridine solution. After heating at 30°-40° for 2 hours, the mixture was left at room temperature overnight. When petroleum ether is added to this mixture, the compound becomes oily and precipitates out. And 50ml of this
Dissolve in 2-methoxyethanol. 1=1 in this solution
Add carbamic acid-N-methyl-hydroxyamine (tetra(N-atiridino))-P-quinone and nitrosoethylamine in the proportions until agglomeration occurs.

It solidifies in about 10ml. When this is dried on filter paper, beautiful pure white crystals are obtained. This product is tasteless, odorless, non-irritating, and carbonizes and decomposes at 180°C. The compound has the following structural formula.

Example 3 2.6 g of P-acetylaminobenzenesulfonyl chloride 1 g of urethane is dissolved in 20 ml of pyridine, heated at 30° to 40° C. for 2 hours, and left overnight.

When petroleum ether is added to this, the compound precipitates out as a liquid. This is separated and hydrolyzed by heating for 15 minutes with 5 times the amount of 15% hydrochloric acid. This hydrolyzate is then separated and dried.

Furthermore, this compound was dissolved in 20 ml of pyridine and heated to 0°C-
While cooling to 5° C., an equivalent amount of dichloroacetyl chloride is added dropwise to combine. After a few hours it is poured onto ice water, resulting in a compound precipitate. Furthermore, this is decomposed and dried.

This dried compound was dissolved in 20 ml of pyridine and 2
Add an equivalent amount of ethyleneimine and heat to 30°C to 40°C for 2 hours.

Furthermore, when this mixture is left at room temperature overnight, the compound precipitates out as a sticky substance at the bottom of the vessel.

The structural formula of the compound obtained here is as shown in the following formula.

This compound is dissolved in 50 ml of 2-methoxyethanol.

Carbaminsan-N-methylformamide ester, 2-chloroethyl methyl ether and 2-chloroethyl methyl ether were added to this in a ratio of 1=1, and Conc magnesium sulfate was further added thereto with stirring until coagulation occurred. Solidify in approximately 10 ml.

The compound obtained here is extremely soluble in water and has a molecular weight of 180
Carbonization decomposes at ℃. Its structural formula is as follows.

Example 4 2.6 g of carbetoquin aminobenzenesulfonyl chloride was dissolved in 40 ml of pyridine, and 1.5 ml was added under cooling.
Gradually add chloromethyl methyl ether to form an oxonium salt.

Leave this at room temperature overnight. Thereafter, petroleum ether is added to this and the compound is obtained as an oily sticky substance.

Wash this oil thoroughly with petroleum ether and add 50 ml of 2-
Dissolved in Methoxy-ethano1 and added 2-
Add chloroethyl N-methylhydroxyamine, then add carbamic acid chloroethyl ester, and add Conc's magnesium sulfate solution while stirring until the solution solidifies. Solidify in approximately 10 ml. When this is dried on filter paper, beautiful water-soluble crystals are formed. This material is carbonized and decomposed at 180°C.

The compound obtained here has the following structural formula.

Example 5 2.6 g of 4-carbetoxin aminobenzenesulfonyl chloride was dissolved in 40 ml of pyridine, and 3 ml of Bis(2-cheoroethyl) 2 et
The mixture is added dropwise under cooling and then heated to 30-40°C for 2 hours.

Then leave it at room temperature overnight. When petroleum ether is added to this mixture, the compound becomes oily and precipitates out. Wash this oxonium compound thoroughly with ether and add 50 ml of 2-Meh.
Conc magnesium sulfate was dissolved in oxy-ethano1, and cytosine carbamate, 2-chloroethylnuthyl ether and (tetra(N-methyl-N-formyl))amino-P-quinone were added thereto in a ratio of 1=1 while stirring. Add solution dropwise until solidified.

Solidify in approximately 10ml. The compound produced here is extremely easily soluble and carbonizes and decomposes at 180°C. The compound has the following structural formula.

Example 6 2.6 g 4-carbethoxyaminobenzenesulfochloride 1 g K1 and 20 ml distilled water are heated to 50° C. for 2 hours with stirring. This is filtered and air-dried.

Dissolve in 2-methoxyethanol. Then, presnisolone carbamate nitrosoethyleneimine (tetra-2-(chloroethyl))amino-P-quinone lysozyme chloride is added in a ratio of 1=1, and while stirring, Conc magnesium sulfate is added until solidified. Solidify in approximately 10 ml.

This compound is a beautiful pure white crystal that is extremely soluble in water.

Carbonized and decomposed at 180°C. The compound obtained here has the following structural formula.

Example 7 2.6g 2-Chloroethylamine After heating to 30°C-40°C for 2 hours, it is left at room temperature overnight. When petroleum ether is added to this mixture, the compound becomes oily and precipitates out. This is separated and heated for 15 minutes in 30 ml of 15% hydrochloric acid to hydrolyze it, and then dried under reduced pressure.

Then, the produced oily substance was dissolved in 5 ml of 2-methoxyethanol, and in this solution, cytosine carbamate, 2-chloroethyl methyl ethertetra(N-methyl-N-formyl)amino-O-quinone was added in a 1=1 ratio. Add the herbal extract and while stirring add the Conc magnesium sulfate until solidified. Solidify in approximately 10ml.

This compound is a beautiful pure white crystal that is extremely soluble in water18
Carbonization decomposes at 0°C. The compound obtained here has the following structural formula.

Example 8 2.6 g 4-carbethoxybenzenesulfonyl chloride was dissolved in 30 ml pyridine and 1 g 2-A
Add minoethane-thiol to 30℃-40
Warm to ℃. Then, leave it at room temperature overnight. After that, when petroleum ether is added, the compound becomes oily and precipitates out. This is separated and dissolved in 2-methoxyethanol. Furthermore, Prednisclo is added to the ratio of 1=1.
ne carbamateClCH2CH2-O-CH
When adding 3 CH(O-NH-CH3)3 and 30-40% magnesium sulfate with stirring, the solution aggregates. It solidifies completely in about 10ml.

When dried on filter paper or air-dried, it becomes pure white, beautiful crystals that are extremely soluble in water, tasteless, odorless, and non-irritating.
Carbonization decomposes at 0°C. The compound obtained here has the following structural formula.

Claims (1)

[Claims] (1) A compound having the following general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ I In the diagram, R and R' are hydrogen, -COCHR^4_2, -CO
CR^4_3-SO_2CH_3-CO_2C_2H_
5, -CH_2CH_2H_4, -CH_2CH_2O
H-CONHCH_2CH_2R^4-CONHCH_
2COOC_2H_5, OderCH_2CH_2OC
Indicates ONH, R^4 is Cl or a compound of the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ Mathematical formulas, chemical formulas,
There are tables etc. ▼ -NHCO_2C_2H_5, -NHOH, -NHCO
Indicates NHOHOder-NHCH_3. R and R' are the same compound or have different structures. In the formula, R^1R^2 is (1) amine ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ mathematical formulas, chemical formulas,
There are tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ -NHCH_2CH_2Cl, -NHCONHOH, -
NHCO_2C_2H_5,6-Mercaptopu
rinyl, 5-Fluoruracilyl, or P
rednisolyl, Salicylhydrazi
dyl, 1-Allyl-2-thiouraclly
l, Hydroxylamine, Isomidyl, or MethyeHydroxylamine (2) Hydroxyl -O-CH_3-O-CH_2-CH_3-O-CH_
2-CH_2-CH_3, -O-C_6-H_5-O-
CH_2-CH-CH_2 or Benzhydrol (3) Ether ClCH_2OCH_2ClCH_3OCH_2CH_
2OCH_3CH_2ClCH_2OCH_2CH_2
ClC_4H_9OCH_3(C_6H_5)_2O▲
There are mathematical formulas, chemical formulas, tables, etc.▼(CH_2=CHCH
_2)_2OCH_2=CHOCH=CH_2C_4H
＿9OC_4H_9C_6H_5OCH_3▲There are mathematical formulas, chemical formulas, tables, etc.▼, ClCH_2OC_2H_5
, OHCH_2CH_2-O-CH_2CH_2Cl,
ClCH_2CHCl-OC_2H_5 ether forms oxonium salt with sulfonyl chloride. (4) ■ indicates an inorganic compound -(Na)SH-(Na)F, -(K)I. Others (5)■ is -(Na)N_3 or -C C-(CI)
Indicates _3 or -(Na)N_3. (b) General scheme (1) can be replaced with alkanesulfonyl chloride (II), or both can be mixed and combined. ▲There are mathematical formulas, chemical formulas, tables, etc.▼II Diagram (II) Indicates a linear hydrocarbon, and the number on the carbon chain indicates the position of the side chain (substituent). (7) The ▲mathematical formula, chemical formula, table, etc. shown in the general scheme (I)▼ group can be substituted with a halogen alkyl group or an aminomethyl group. In the case of an aminomethyl group, it has the following structural formula. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Mt shown in general diagram (1) indicates metal. 2. When producing the clathrate compound of the above general formula 1 (1) (
Claim 1 as an inclusion gest with anticancer agents) nitromine, cyclophosphamide, thiotepa, 6-mercaptopurine, 5-fluorouracil, pinplastin, L-asparaginase, or prednisolone, etc.
Method 3 for producing a clathrate compound produced according to (2) (2) (
Antibiotics) Method 4 for producing a clathrate compound produced according to claim 1 with chloramphenicol, streptomycin, penicillin, etc. as a clathrate gest, when producing the clathrate compound of the above general formula 1 (3) )(
Method 5 for producing a clathrate compound produced according to claim 1 as an inclusion gest with pyoctanine (methyl violet), methylene blue, acriflapine, etc. (pigments with medical effects), producing a clathrate compound of the above general formula 1 If (4) (
Claim 1 as an inclusion gest containing general organic compounds) sality hydratide, thiodinamine, glycoseed, resorcin, chlorpheniramine maleate, abscisic acid, cytosine, N-methylformamide, urethane, glycoside, medicinal herbal extract, etc. Method 6 for producing an clathrate compound produced according to the above, in the case of producing the clathrate compound of the above general formula 1 (5) Inorganic/substance) Inclusion gest with Zm, Hg, Cu, Pd, Pt salt or Au salt, etc. Method 7 for producing an clathrate compound produced according to claim 1 as a molecule, when producing the clathrate compound of the above general formula 1 (6) (
Nitroso Compounds) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ▲There are mathematical formulas, chemical formulas, tables, etc.▼ etc. are used as inclusion gest molecules in Method 8 of the production of clathrate compounds produced according to claim 1, above. When producing the clathrate compound of general formula 1 (7) (
Enzyme) Inclusion gest with hyalnitase, lysozyme, collagenase, sulfatase or pectinase, diastase and other immobilized enzymes, especially metalloenzymes, etc.
Method 9 for producing an clathrate compound produced according to claim 1, in the case of producing the clathrate compound of the above general formula 1 (8) (
Hormones) Androgenes, Adrenoco
rtiKal Hormones, Estrogens,
Method 10 for producing an clathrate compound according to claim 1 as an clathrate gest molecule, when producing an clathrate compound of the above general formula (9) (
c aquinones) (Tetra-2 (Chlorethyl) amino
)-o-guinone(Tetra(N-methy
l-N-formyl)amino)-o-gnino
ne(Tetra(N-Carboethoxy)am
ino)-o-gninone(Tetra(N-az
iridio))-o-gninone(Tetra(
N-methyl-N-hydroxyl)amino
)-gninone etc. as an inclusion gest molecule in accordance with claim 1. Method 11 for producing the clathrate compound of the above general formula (10)
(Carbamate esters) ▲Mathematical formulas, chemical formulas, tables, etc.▼、▲Mathematical formulas, chemical formulas,
There are tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ Mathematical formulas, chemical formulas,
There are tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Manufactured according to claim 1 as an inclusion gest molecule Method 12 for producing a clathrate compound of the above general formula (11)
2-Chloroethyl compound ChloralKylDerivatives, Cl-
CH_2・CH_2-O-CH_3, Cl-CH_2・
▲There are mathematical formulas, chemical formulas, tables, etc.▼Cl, CH_2CH
_2-NH-OH, Cl-CH_2・▲There are mathematical formulas, chemical formulas, tables, etc.▼ Cl-CH_2・▲There are mathematical formulas, chemical formulas, tables, etc.▼ Manufactured according to claim 1 as an inclusion gest with a rod Method 13 for producing clathrate compounds, a method for producing clathrate compounds according to claim 1 by combining the clathrate components described in claims 1 to 12 with a metal salt in a flocculating solvent. 14. A method for preparing a preparation containing the clathrate compounds produced according to claims 1-12 alone or in combination as active ingredients.